Biphenyl-4-Carboxylic Acid Derived Esters with Antifungal Activity

Rayanne Hellen do Nascimento S

Abstract

Candidiasis presents as either a superficial or systemic fungal infection caused by Candida yeast species. Immunocompromised patients such as HIV infected individuals, carriers of chronic disease, diabetics and transplanted patients, as well as the elderly and newborns are the groups with the greatest susceptibility to such infections. Some species of this genus have shown resistance to a wide range of antifungal agents, increasing both infection severity and complexity of treatment. In this work, a collection of biphenyl-4-carboxylic acid ester derivatives was prepared, and the activity of these compounds was investigated against pathogenic species of the Candida genus. Both Fischer esterification and so-called non-Fischer esterification using alkyl halides were employed to prepare the esters. Antifungal assays were performed using broth microdilution methods. The main objective of this work was to trace structure-activity relations for the compounds obtained. Of the eight esters prepared in this study, four presented activity against strains of Candida albicans and Candida tropicalis. The substances yielded good to moderate bioactivities. The bioactivities found amongst the evaluated esters for the tested strains were highest for ethyl 4-biphenyl carboxylate (obtaining MICs ranging from 512 to 1024 μg/mL); and decanoyl 4-biphenyl carboxylate (obtaining an MIC of 512 μg/mL). All of the molecules presenting either a heteroatom or bulky groups close to the ester function demonstrated bioactivity.